Chemerin induces endothelial cell inflammation: activation of nuclear factor-kappa beta and monocyte-endothelial adhesion

// Georgios K. Dimitriadis 1, 2, 3, * , Jaspreet Kaur 1, 4, * , Raghu Adya 1 , Alexander D. Miras 2 , Harman S. Mattu 1 , John G. Hattersley 3 , Gregory Kaltsas 3 , Bee K. Tan 1, 5 and Harpal S. Randeva 1, 3, 6 1 Division of Translational and Experimental Medicine, Warwick Medical School, University of Warwick, Coventry, UK 2 Division of Endocrinology and Experimental Medicine, Imperial College London, Hammersmith Campus, London, UK 3 WISDEM Centre, Human Metabolism Research Unit, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK 4 Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA 5 Department of Obstetrics and Gynaecology, Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, UK 6 Division of Life and Health Sciences, Aston University, Birmingham, UK * These are joint first authors Correspondence to: Harpal S. Randeva, email: Harpal.Randeva@warwick.ac.uk Keywords: chemerin; T2DM; atherosclerosis; endothelium; inflammation Received: January 15, 2018      Accepted: February 27, 2018     Published: March 30, 2018 ABSTRACT Chemerin, a chemoattractant protein, acts via a G-protein coupled chemokine receptor, i.e. Chemokine like Receptor 1/ChemR23; levels of which are elevated in pro-inflammatory states such as obesity and type 2 diabetes mellitus (T2DM). Obesity and T2DM patients are at high risk of developing cardiovascular disorders such as atherosclerosis. We have reported that chemerin induces human endothelial cell angiogenesis and since dysregulated angiogenesis and endothelial dysfunction are hallmarks of vascular disease; we sought to determine the effects of chemerin on monocyte-endothelial adhesion, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a critical pro-inflammatory transcription factor. Human endothelial cells were transfected with pNF-kappaB-Luc plasmid. Chemerin induced NF-κB activation via the MAPK and PI3K/Akt pathways. Western blot analyses and monocyte-endothelial adhesion assay showed that chemerin increased endothelial cell adhesion molecule expression and secretion, namely E-selectin (Endothelial Selectin), VCAM-1 (Vascular Cell Adhesion Molecule-1) and ICAM-1 (Intracellular Adhesion Molecule-1), leading to enhancement of monocyte-endothelial adhesion. Additionally, we showed a synergistic response of the pro-inflammatory mediator, Interleukin-1β with chemerin induced effects. Chemerin plays an important role in endothelial inflammation, as it induces monocyte-endothelial adhesion, a critical step in the development of atherosclerosis.